Explanation and prediction for the crystallized products from amorphous bicalutamide and bicalutamide solutions by using mid-frequency Raman difference spectra

Abstract

Bicalutamide (BIC) is one fluorine-containing drug with poor aqueous solubility, and it is essential to study the polymorphism of BIC, especially the metastable polymorphs and amorphous phase, to improve the oral effect. Selective crystallizations of BIC amorphous phases and solutions were studied and further explained and predicted by using mid-frequency Raman difference spectra (MFRDS) here. The relationships among various polymorphs and solutions of BIC were established by calculating the values of average deviation (a. d., the average value of absolute value of the intensity of MFRDS) and standard deviation (s. d.) of the MFRDS. And the possible routes to obtain metastable Form II and amorphous BIC were proposed based on the MFRDS results. Metastable Form II can be obtained by recrystallization of the amorphous BIC prepared through melt-quenching method. Amorphous BIC without additives can be prepared through a quicky evaporation process of acetone and ethyl acetate solutions, which was reported for the first time. The MFRDS results confirmed the presence of residual acetone and ethyl acetate in amorphous BIC obtained by evaporation, and the residual solvents changed the recrystallization products of amorphous BIC. MFRDS analysis can be a useful tool to guide the preparation and selective crystallization of metastable polymorphs and amorphous phase.